EXTH-16. THE ORAL IRON-MIMETIC GALLIUM MALTOLATE SUPPRESSES TREATMENT-RESISTANT GLIOBLASTOMA – IN VIVO VALIDATION

Abstract

Abstract BACKGROUND We previously reported on our in vitro and in vivo studies using the metallocompound gallium maltolate (GaM) to target glioblastoma (GBM). We demonstrated a profound cytotoxic effect in vitrov and in vivo. Additionally, our preliminary in vivo data suggested a substantial inhibitory effect on tumor growth, as well as a significant extension of disease-specific survival (OS). Here, we further validate the inhibitory effects of GaM in vivo. METHODS In vitro irradiated adult GBM U87-MG cells were stereotactically implanted into the right striatum of male and female athymic rats. Advanced MR imaging at 9.4T was carried out weekly starting two weeks after implantation. Daily oral GaM (50 mg/kg) or vehicle were provided on tumor confirmation. Longitudinal advanced MRI parameters were processed for enhancing tumor ROIs in OsiriX 8.5.1 (lite) with Imaging Biometrics Software (Imaging Biometrics LLC,). Statistical analyses included Kaplan-Meier survival plots, linear mixed model (LMM) comparisons, and t-statistic for slopes comparison (as indicator of tumor growth rate). RESULTS Median OS for the male pilot cohort (5 control, 5 GaM) was 28 and 51 days, respectively; 31 and 59 days for the male replication cohort (1 control, 3 GaM); 37 and 48 days for the female replication cohort (6 control, 7 GaM). GaM-treated xenograft tumors grew significantly slower than control tumors with sex and time dependent growth rates. No significant differences were seen between male and female cohorts in both control and treatment groups at all timepoints. Hence, subsequent analyses were performed on pooled data. Median OS was 30.5 days and 48 days for control and GaM groups, respectively (p < .001). A strong correlation between treatment and survival (Χ2 = 6.238187; p = .0125) and tumor growth suppression (LMM; p < .0001) was evident. CONCLUSION We have successfully validated the inhibitory effects of GaM on GBM growth in vivo.